Project-2 Summary/Abstract: The prevalence of Alzheimer's disease (AD) is closely related to the presence of cardiovascular disease (CaVD), understanding the relationship between AD pathology and CaVD is critically important. In the competing renewal of this Program Project (PPG3), we will explore whether our finding related to CaVD and A? pathology in a very elderly cohort will apply to a more diverse cohort. The overarching goal of Project 2 of PPG3 is to further the understanding of the relationship between AD pathology and midlife CaVD and the impact of these factors on cognitive impairment in a group of young old. To achieve these goals, we will utilize a group non-demented participants from an existing cohort from the ongoing community-based Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study, a longitudinal study that began in 2003 with a cohort of 2000 participants (43% African American) between the ages of 45-75 years at study entry and has collected a wealth of longitudinal vascular measures. This study will explore two main hypotheses explore two hypotheses: 1) CaVD and amyloid-beta (A?) deposition are independent predictors of cognitive decline, and increased CaVD creates a state of vulnerability by interfering with vascular-related compensatory mechanisms; and 2) CaVD accelerates A? deposition in the brain, thus accelerating the onset of clinical symptoms. The findings from this study will help to further inform our understanding of the relationship between vascular pathology and AD pathology in midlife.